This document corcerns as invention relating generally to mounting/gripping apparata for use in the handling and manipulation of microtools (i.e., precision instruments and manipulators for microtechnology and nanotechnology applications, such as fluid-transporting microcapillaries), and more specifically to mounting apparata for quickly and safely receiving and releasing fragile microcapillaries.
Capillaries are commonly used in biological applications to sample and transport fluids and/or cells for testing or other purposes. When particularly fine biological microoperations are requiredxe2x80x94for example, injecting or removing cellular genetic material during in vitro fertilization or cloning operationsxe2x80x94microcapillaries are generally used. Microcapillaries are ordinarily prepared by taking a standard glass capillary tube (usually having 1 millimeter diameter), and heating it until it becomes ductile. The capillary is then stretched, causing its diameter to contract. When the capillary is stretched to the desired diameter, generally around 10 microns (inner diameter), it is cooled and allowed to set. The microcapillary""s leading edge may then be ground to a point by use of a microgrinder so that it has a sharp leading edge suitable for puncturing a cell membrane.
The microcapillary may then be inserted into the cell, and by decreasing the pressure at the end of the microcapillary, the desired cellular material may be aspirated into the microcapillary. Naturally, such an operation requires very precise control over the positioning of the microcapillary, and therefore mounting/positioning arrangements such as the one shown in FIG. 1 are commonly used. Cellular material is placed on a sampling plate 10 (e.g., a Petri dish or the like). A microscope 12 (or other imaging apparatus) adjacent the sampling plate 10 allows viewing of cells as they are being manipulated. The microcapillary 50 is gripped with a mount 14, with its tip 52 at or slightly above the sampling plate 10. The mount 14 is mounted to an actuator 16, which allows the mount 14 to reposition the microcapillary 50 in at least one dimension in relation to the sampling plate 10 by manipulating a joystick 18 or other input device. A flexible tube 54 fit over the end of the microcapillary 50 leads to a syringe 20 or similar injection device so that suction can be applied to the microcapillary 50. Thus, a user may use the joystick 18 to position the microcapillary 50 as desired, and may use the syringe 20 to withdraw or inject cellular material from or to the cell(s) on the sampling plate 10 when the microcapillary 50 is appropriately positioned.
Problems can occur owing to the attachment between the microcapillary 50 and mount 14, an arrangement which is shown in greater detail in FIG. 2. In general, the mount 14 bears a V-groove 22 wherein the microcapillary 50 may be situated, and a screw-driven clamp 24 is adjusted to bear against the microcapillary 50 and hold it within the groove 22. While this arrangement is simple to manufacture, operate, and maintain, it causes several significant difficulties with use of the microcapillary 50.
First, it is exceedingly easy to either tighten the clamp 24 to such an extent that the microcapillary 50 is crushed, or to conversely leave the clamp 24 so loose that the microcapillary 50 slips within the groove. Breakage is highly inconvenient because the microcapillaries 50 take a long time to prepare, and are usually prepared right before an operation is to be performed to ensure that the microcapillaries 50 are uncontaminated with foreign matter. Since microcapillaries 50 are difficult to properly form and grind and it may take several tries before a suitable microcapillary 50 is obtained, lab personnel generally do not produce a large number of them; therefore, if the available microcapillaries 50 break, lab personnel may be set back by an hour or more as new ones are prepared. This delay may be costly since the cellular material to be operated on may have a limited time window of viability.
Second, the clamp 24 is somewhat time-consuming to deal with. As previously noted, the user must take care when placing a microcapillary 50 in the clamp 24 to be sure that the clamp 24 is neither too loose nor too tight. Further, it is desirable to have a microcapillary 50 which is at least generally well-positioned over the sampling plate 10 prior to the start of the operation: for example, it may be desirable to have it extend from the clamp 24 at or near a certain length, with its sharpened tip 52 being oriented at or near a desired angle. However, to reposition the microcapillary 50 within the clamp 24, the clamp 24 must be unscrewed, the microcapillary 50 must be repositioned, and then the clamp 24 must be carefully screwed down again. These repositioning activities provide further opportunities for lost time and broken microcapillaries 50.
Third, the mount 14 is difficult to use because the user must hold the microcapillary 50 in one hand and simultaneously tighten the clamp 24. Because this is difficult to do with only two hands, the user often initially situates the clamp 24 in an improper position, and must then undergo the aforementioned iterative process of loosening the clamp 24, adjusting the microcapillary 50, and retightening the clamp 24 until the microcapillary 50 is properly positioned.
Since there is an increasing need for speedy and accurate operations on biological materials, particularly where the biological materials have time-limited viability, it would be advantageous to have available a microcapillary mount which overcomes the disadvantages of the prior mounts, and which allows for fast mounting, alignment, and release of microcapillaries, while minimizing the possibility of microcapillary breakage.
The invention, which is defined by the claims set forth at the end of this document, is directed to mounts for microtools (e.g., microcapillaries) which at least partially alleviate the aforementioned problems. A basic understanding of some of the preferred features of the invention can be attained from a review of the following brief summary of the invention, with more details being provided elsewhere in this document.
To summarize, the microtool mount (as best seen in the different embodiments of FIGS. 3-5) includes an elongated finger terminating in a tip. The finger has a pair of valley edges from which valley walls descend to terminate in a valley floor, thereby defining a valley between the valley walls and floor. The valley extends from the tip along a path parallel to at least a portion of the length of the finger. A microcapillary may be accommodated within the valley (see particularly FIGS. 3 and 4), and a fastening member, preferably a magnet, may be removably affixed to the finger above the valley to maintain the microcapillary within the valley. The valley edges are preferably planar along at least a portion of the length of the finger so as to provide an even surface whereupon the magnet may be more firmly affixed to the finger. The valley is preferably situated within the finger so that a microcapillary resting therein will be aligned with the longitudinal axis of the finger, so that rotation of the finger about this longitudinal axis will also cause the microcapillary to rotate about its longitudinal axis. This allows for greater ease in positioning the microcapillary at desired locations during a biological operation.
In certain preferred embodiments (such as those of FIGS. 4 and 5), at a location spaced rearward of the tip of the finger, one or more of the valley edges has a ledge from which the valley edge begins descending towards the valley floor. A gap is thereby defined in this valley edge and its valley wall. Such a gap may be defined in both valley edges/walls, as illustrated in FIG. 4, or the gap may be defined in one valley edge/wall, as illustrated in FIG. 5. This gap (or gaps) may therefore define a depressed pit spaced rearward from the tip of the finger, behind the mounting surface for the fastening member. The pit provides an enlarged area which better accommodates any flexible lead (e.g., an elastomeric tube, or a flexible wire) trailing from the end of a microtool maintained within the valley, and which allows easier egress of the lead from the finger (see particularly FIG. 4). As illustrated best by the embodiment of FIG. 6 (also shown in FIG. 5), the pit (the element labeled 324 in FIG. 6) may be depressed within the valley so that the length of a microcapillary resting forward of the lead will be cradled within the valley, and the portion of the lead which is fit over the end of the microcapillary will not bias the end of the microcapillary partially out of the valley.
As exemplified by the embodiment of FIG. 5, the valley edges may be formed in two sections, with a distal lower region adjacent to the tip and a proximal raised region spaced from the tip and separated from the lower region by a ledge. A fastening member accommodated on the lower region can therefore be accommodated against the ledge for greater resistance against slipping.
The finger preferably includes a rodlike proximal end opposite the tip, with this proximal end being rotatably journalled within a micromanipulator clip or the like to allow the finger to rotate about the axis of the finger. It is beneficial to situate the valley such that it is coincident with the rotational axis of the finger, so that rotation of the finger about the rotational axis will rotate the microcapillary (or other microtool) about its lengthwise axis as well.
The invention is exceedingly useful for mounting microcapillaries in biological applications such as IVF (in vitro fertilization), particularly ICSI (introcytoplasmic sperm injection); in cloning, where genetic material must be injected or removed; in transgenic technologies; in manipulation of chromosomes; in intracellular electrophysiology; and in so-called xe2x80x9cpatch clumpingxe2x80x9d systems. However, the invention may be utilized with numerous microtools apart from microcapillaries, such as microelectrodes, microprobes, nanotips or the like, and may be used in nonbiological operations, e.g., scanning probe microscopy.
Further advantages, features, and objects of the invention will be apparent from the following detailed description of the invention in conjunction with the associated drawings.